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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 235 records · Page 13
All sourcesNASA NTRSDOE OSTI
DOE OSTI2013

Abdominal-B and caudal inhibit the formation of specific neuroblasts in the Drosophila tail region

The central nervous system of Drosophila melanogaster consists of fused segmental units (neuromeres), each generated by a characteristic number of neural stem cells (neuroblasts). In the embryo, thoracic and anterior abdominal neuromeres are almost equally sized and formed by repetitive sets of neuroblasts, whereas the terminal abdominal neuromeres are generated by significantly smaller populations of progenitor cells. Here we investigated the role of the Hox gene Abdominal-B in shaping the terminal neuromeres. We show that the regulatory isoform of Abdominal-B (Abd-B.r) not only confers abdominal fate to specific neuroblasts (e.g. NB6-4) and regulates programmed cell death of several progeny cells within certain neuroblast lineages (e.g. NB3-3) in para-segment 14, but also inhibits the formation of a specific set of neuroblasts in para-segment 15 (including NB7-3). We further show that Abd-B.r requires cooperation of the ParaHox gene caudal to unfold its full competence concerning neuroblast inhibition and specification. Thus, our findings demonstrate that combined action of Abdominal-B and caudal contributes to the size and composition of the terminal neuromeres by regulating both the number and lineages of specific neuroblasts.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Data for "Efficient Mutagenesis and Genotyping of Maize Inbreds Using Biolistics, Multiplex CRISPR/Cas9 Editing, and Indel-Selective PCR"

CRISPR/Cas9 based genome editing has advanced our understanding of a myriad of important biological phenomena. Important challenges to multiplex genome editing in maize include assembly of large complex DNA constructs, few genotypes with efficient transformation systems, and costly/labor-intensive genotyping methods. Here we present an approach for multiplex CRISPR/Cas9 genome editing system that delivers a single compact DNA construct via biolistics to Type I embryogenic calli, followed by a novel efficient genotyping assay to identify desirable editing outcomes. We first demonstrate the creation of heritable mutations at multiple target sites within the same gene. Next, we successfully created individual and stacked mutations for multiple members of a gene family. Genome sequencing found off-target mutations are rare. Multiplex genome editing was achieved for both the highly transformable inbred line H99 and Illinois Low Protein1 (ILP1), a genotype where transformation has not previously been reported. In addition to screening transformation events for deletion alleles by PCR, we also designed PCR assays that selectively amplify deletion or insertion of a single nucleotide, the most common outcome from DNA repair of CRISPR/Cas9 breaks by non-homologous end-joining. The Indel-Selective PCR (IS-PCR) method enabled rapid tracking of multiple edited alleles in progeny populations. The ‘end to end’ pipeline presented here for multiplexed CRISPR/Cas9 mutagenesis can be applied to accelerate maize functional genomics in a broader diversity of genetic backgrounds.

gene editing↗
DOE OSTI2013

When Is the Simple Radiotoxicity Approach Useful for Advanced Fuel Cycle System Assessments Given the Existence of Complex Performance Dose Assessments?

Engineers often face the general question of which approximations are appropriate for a given analytical task. In particular, when is a simpler model useful if a more complex model also exists? This paper explores this question in the domain of radiotoxicity relative to geologic disposal performance dose assessments. Criterion 1 requires that the simpler approach, radiotoxicity, must be calculated correctly. The concept of ingestion radiotoxic inventories is analogous to the inventory of toxic chemicals in other industries. From a decision analysis perspective, it is also somewhat analogous to the nuclear reactor safety concept of “passive safety.” This paper explains some of the issues in calculating radiotoxicity, motivated by the author’s observations of errors in the literature: not accounting for radioactive progeny, misunderstanding natural “ore,” and focusing on transuranic (TRU) isotopes without adequate attention to actinide decay products. For example, Th/233U fuel cycles do have lower amounts of TRU isotopes than U/239Pu fuel cycles, but that does not necessarily mean lower long-term hazard. Criterion 2 requires that the uncertainties in the more complex approach, performance dose assessments, must raise issues for the assessments’ intended purposes—in which case, radiotoxic inventory may be of assistance until those issues are resolved. Performance dose assessments were developed for, and are legally the way to show, compliance with regulations, but the uncertainties are large. Less obvious is the degree to which dose assessments are applicable to other purposes—comparing fuel cycle options prior to site selection and showing the safety of a fuel cycle and waste management approach to the public. In the last sense especially, performance dose assessments are analogous to probabilistic risk assessments for nuclear reactor safety. The United States lacks a selected consensus site, selected fuel cycle approach (direct disposal versus recycling), and selected waste form. Thus, the paper does not intend to discuss all the issues with performance dose assessments but rather intends to focus on only those performance dose uncertainties that raise issues when comparing fuel cycles. Uncertainties associated with whether a generic geological environment is attractive or a specific location meets requirements are beyond the scope of this paper. Ingestion radiotoxicity correlates with heat, gamma, and inhalation radiotoxicity. Thus, options that are relatively high in ingestion radiotoxicity tend to be high in other parameters. Therefore, reduction in ingestion radiotoxicity means both that the potential source term for release is lower but also that one driving force for release (heat) is also lower. However, the most important time frames differ as heat is mainly an issue in decades and centuries after reactor discharge, but ingestion radiotoxicity is mainly an issue during longer time periods. Ingestion radiotoxicity points to the importance of actinides in long-term waste management, followed by specific fission products such as 99Tc, 129I, 93Zr, 135Cs, and 79Se.

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗
DOE OSTI2015

Computational Assessment of Naturally Occurring Neutron and Photon Background Radiation Produced by Extraterrestrial Sources

In this study, a computational assessment of the variation in terrestrial neutron and photon background from extraterrestrial sources is presented. The motivation of this assessment is to evaluate the practicality of developing a tool or database to estimate background in real time (or near–real time) during an experimental measurement or to even predict the background for future measurements. The extraterrestrial source focused on during this assessment is naturally occurring galactic cosmic rays (GCRs). The MCNP6 transport code was used to perform the computational assessment. However, the GCR source available in MCNP6 was not used. Rather, models developed and maintained by NASA were used to generate the GCR sources. The largest variation in both neutron and photon background spectra was found to be caused by changes in elevation on Earth's surface, which can be as large as an order of magnitude. All other perturbations produced background variations on the order of a factor of 3 or less. The most interesting finding was that ~80% and 50% of terrestrial background neutrons and photons, respectively, are generated by interactions in Earth's surface and other naturally occurring and man-made objects near a detector of particles from extraterrestrial sources and their progeny created in Earth's atmosphere. In conclusion, this assessment shows that it will be difficult to estimate the terrestrial background from extraterrestrial sources without a good understanding of a detector's surroundings. Therefore, estimating or predicting background during a measurement environment like a mobile random search will be difficult.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗
DOE OSTI2022

Impact of Increased Latent Generations on Sensitivity Calculations with SCALE

Analyses of cross section sensitivity data from systems with fissile material allow analysts to associate an importance for each material, nuclide, reaction, and neutron energy by simulating real world criticality scenarios. Although criticality safety validation efforts can be guided by the cross-section sensitivity and uncertainty data generated for a particular system, these calculations can often be computationally expensive and sometimes cumbersome without proper guidance. The TSUNAMI suite within the SCALE code package has several methods for generating sensitivity data, including multigroup and continuous energy (CE) capabilities. The release of SCALE 6.3 has three different CE methods for generating cross section sensitivity data: (1) the Iterated Fission Probability (IFP) method with the KENO Monte Carlo transport solver, (2) the IFP method with the Shift Monte Carlo transport solver, and (3) the Contributon-Linked eigenvalue sensitivity/Uncertainty estimation via Tracklength importance CHaracterization (CLUTCH) method with the KENO Monte Carlo transport solver. Although the CLUTCH method has additional parameters for generating sensitivity data files relative to the IFP method, all three methods use latent generations, which are the generations between an event (i.e., fission) and the assessment of importance based on the asymptotic population of progeny neutrons. Increasing the number of latent generations in a calculation leads to increased discrimination of the sensitivity coefficients but at the cost of the increased uncertainty associated with those generated values. Analysts must balance the accuracy of the sensitivity calculations and its uncertainty with the associated computational cost involved in generating the values. This paper discusses the impact of adjusting the latent generation parameter for a range of sensitivity values and how these changes compare with the direct perturbation values obtained from a change of ±0.5% Δ k in both benchmark and safety application models. Two benchmarks from the International Handbook of Evaluated Criticality Safety Benchmark Experiments and the MPC-32 dual purpose canister for spent nuclear fuel are used for analysis.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗
DOE OSTI2013

Genome anchored QTLs for biomass productivity in Hybrid Populus: Heterosis and detection across Contrasting Environments.

Traits related to biomass production were analyzed for the presence of quantitative trait loci (QTLs) in an interspecific F2 population derived from an outbred Populus trichocarpa P. deltoides parental cross. Three years of phenotypic data for stem growth traits (height and diameter) were collected from two parental, two F1 and 339 F2 trees in a clonal trial replicated both within and among two environmentally contrasting sites in the North American Pacific Northwest. A genetic linkage map comprised of 841 SSR, AFLP, and RAPD markers and phenotypic data from 310 progeny were used to identify genomic regions harboring QTL using the Multiple-QTL Model (MQM) package of the statistical program MapQTL 6. A total of twelve QTLs, nine putative and three suggestive, were identified with eight of these being identified at both sites in at least one experiment. Of these, three putative QTL BM-1, BM-2, BM-7, on LGs I, II, and XIV, respectively, were identified in all three years for both height and diameter. Two QTLs BM-2 and BM-7, on LG II and XIV, respectively, exhibited significant evidence of over-dominance in all three years for both traits. Conversely a QTL on BM-6 LG XIII exhibited out-breeding depression in two years for both height and diameter. The remaining nine QTLs showed difference levels of dominance and additive effects. Seven of the nine QTL were successfully anchored and QTL peak positions were estimated for each one on the P. trichocarpa genome assembly using flanking SSR markers with known physical positions positions. QTL BM-7 on LG XIV had been anchored on the genome assembly in a previous study, therefore eight QTLs identified in this study were assigned genome assembly positions. Physical distances encompassed by each QTL regions ranged from 1.3 to 8.8 Mb.

Muchero, Wellington↗
DOE OSTI2014

The Role of IKKβ in Venezuelan Equine Encephalitis Virus Infection

Venezuelan equine encephalitis virus (VEEV) belongs to the genus Alphavirus, family Togaviridae. VEEV infection is characterized by extensive inflammation and studies from other laboratories implicated an involvement of the NF-kB cascade in the in vivo pathology. Initial studies indicated that at early time points of VEEV infection, the NF-kB complex was activated in cells infected with the TC-83 strain of VEEV. One upstream kinase that contributes to the phosphorylation of p65 is the IKKb component of the IKK complex. Our previous studies with Rift valley fever virus, which exhibited early activation of the NF-kB cascade in infected cells, had indicated that the IKKb component underwent macromolecular reorganization to form a novel low molecular weight form unique to infected cells. This prompted us to investigate if the IKK complex undergoes a comparable macromolecular reorganization in VEEV infection. Size-fractionated VEEV infected cell extracts indicated a macromolecular reorganization of IKKb in VEEV infected cells that resulted in formation of lower molecular weight complexes. Well-documented inhibitors of IKKb function, BAY-11-7082, BAY-11-7085 and IKK2 compound IV, were employed to determine whether IKKb function was required for the production of infectious progeny virus. A decrease in infectious viral particles and viral RNA copies was observed with inhibitor treatment in the attenuated and virulent strains of VEEV infection. In order to further validate the requirement of IKKb for VEEV replication, we overexpressed IKKb in cells and observed an increase in viral titers. In contrast, studies carried out using IKKb -/- cells demonstrated a decrease in VEEV replication. In vivo studies demonstrated that inhibitor treatment of TC-83 infected mice increased their survival. Finally, proteomics studies have revealed that IKKb may interact with the viral protein nsP3. In conclusion, our studies have revealed that the host IKKb protein may be critically involved in VEEV replication.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2014

Efficient CRISPR/Cas9-Mediated Gene Editing in Arabidopsis thaliana and Inheritance of Modified Genes in the T2 and T3 Generations

The newly developed CRISPR/Cas9 system for targeted gene knockout or editing has recently been shown to function in plants in both transient expression systems as well as in primary T1 transgenic plants. However, stable transmission of genes modified by the Cas9/single guide RNA (sgRNA) system to the T2 generation and beyond has not been demonstrated. Here we provide extensive data demonstrating the efficiency of Cas9/sgRNA in causing modification of a chromosomally integrated target reporter gene during early development of transgenic Arabidopsis plants and inheritance of the modified gene in T2 and T3 progeny. Efficient conversion of a nonfunctional, out-of-frame GFP gene to a functional GFP gene was confirmed in T1 plants by the observation of green fluorescent signals in leaf tissues as well as the presence of mutagenized DNA sequences at the sgRNA target site within the GFP gene. All GFP-positive T1 transgenic plants and nearly all GFP-negative plants examined contained mutagenized GFP genes. Analyses of 42 individual T2 generation plants derived from 6 different T1 progenitor plants showed that 50% of T2 plants inherited a single T-DNA insert. The efficiency of the Cas9/sgRNA system and stable inheritance of edited genes point to the promise of this system for facile editing of plant genes.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2018

Genetic stability of foot-and-mouth disease virus during long-term infections in natural hosts

Foot-and-mouth disease (FMD) is a severe infection caused by a picornavirus that affects livestock and wildlife. Persistence in ruminants is a well-documented feature of Foot-andmouth disease virus (FMDV) pathogenesis and a major concern for disease control. Persistently infected animals harbor virus for extended periods, providing a unique opportunity to study within-host virus evolution. This study investigated the genetic dynamics of FMDV during persistent infections of naturally infected Asian buffalo. Using next-generation sequencing (NGS) we obtained 21 near complete FMDV genome sequences from 12 sub-clinically infected buffalo over a period of one year. Four animals yielded only one virus isolate and one yielded two isolates of different serotype suggesting a serial infection. Seven persistently infected animals yielded more than one virus of the same serotype showing a longterm intra-host viral genetic divergence at the consensus level of less than 2.5%. Quasi-species analysis showed few nucleotide variants and non-synonymous substitutions of progeny virus despite intra-host persistence of up to 152 days. Phylogenetic analyses of serotype Asia-1 VP1 sequences clustered all viruses from persistent animals with Group VII viruses circulating in Pakistan in 2011, but distinct from those circulating on 2008–2009. Furthermore, signature amino acid (aa) substitutions were found in the antigenically relevant VP1 of persistent viruses compared with viruses from 2008–2009. Intra-host purifying selective pressure was observed, with few codons in structural proteins undergoing positive selection. However, FMD persistent viruses did not show a clear pattern of antigenic selection. Our findings provide insight into the evolutionary dynamics of FMDV populations within naturally occurring subclinical and persistent infections that may have implications to vaccination strategies in the region.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

A size-invariant bud-duration timer enables robustness in yeast cell size control

Cell populations across nearly all forms of life generally maintain a characteristic cell type-dependent size, but how size control is achieved has been a long-standing question. The G1/S boundary of the cell cycle serves as a major point of size control, and mechanisms operating here restrict passage of cells to Start if they are too small. In contrast, it is less clear how size is regulated post-Start, during S/G2/M. To gain further insight into post-Start size control, we prepared budding yeast that can be reversibly blocked from bud initiation. While blocked, cells continue to grow isotropically, increasing their volume by more than an order of magnitude over unperturbed cells. Upon release from their block, giant mothers reenter the cell cycle and their progeny rapidly return to the original unperturbed size. We found this behavior to be consistent with a size-invariant 'timer' specifying the duration of S/G2/M. These results indicate that yeast use at least two distinct mechanisms at different cell cycle phases to ensure size homeostasis.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2019

Proximity-dependent proteomics of the Chlamydia trachomatis inclusion membrane reveals functional interactions with endoplasmic reticulum exit sites

Chlamydia trachomatis is the most common bacterial sexually transmitted infection, responsible for millions of infections each year. Despite this high prevalence, the elucidation of the molecular mechanisms of Chlamydia pathogenesis has been difficult due to limitations in genetic tools and its intracellular developmental cycle. Within a host epithelial cell, chlamydiae replicate within a vacuole called the inclusion. Many Chlamydia –host interactions are thought to be mediated by the Inc family of type III secreted proteins that are anchored in the inclusion membrane, but their array of host targets are largely unknown. To investigate how the inclusion membrane proteome changes over the course of an infected cell, we have adapted the APEX system of proximity-dependent biotinylation. APEX is capable of specifically labeling proteins within a 20 nm radius in living cells. We transformed C. trachomatis to express the enzyme APEX fused to known inclusion membrane proteins, allowing biotinylation and pull-down of inclusion-associated proteins. Using quantitative mass spectrometry against APEX labeled samples, we identified over 400 proteins associated with the inclusion membrane at early, middle, and late stages of epithelial cell infection. This system was sensitive enough to detect inclusion interacting proteins early in the developmental cycle, at 8 hours post infection, a previously intractable time point. Mass spectrometry analysis revealed a novel, early association between C. trachomatis inclusions and endoplasmic reticulum exit sites (ERES), functional regions of the ER where COPII-coated vesicles originate. Pharmacological and genetic disruption of ERES function severely restricted early chlamydial growth and the development of infectious progeny. APEX is therefore a powerful in situ approach for identifying critical protein interactions on the membranes of pathogen-containing vacuoles. Furthermore, the data derived from proteomic mapping of Chlamydia inclusions has illuminated an important functional role for ERES in promoting chlamydial developmental growth.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Novel viruses of the family Partitiviridae discovered in Saccharomyces cerevisiae

It has been 49 years since the last discovery of a new virus family in the model yeast Saccharomyces cerevisiae . A large-scale screen to determine the diversity of double-stranded RNA (dsRNA) viruses in S . cerevisiae has identified multiple novel viruses from the family Partitiviridae that have been previously shown to infect plants, fungi, protozoans, and insects. Most S . cerevisiae partitiviruses (ScPVs) are associated with strains of yeasts isolated from coffee and cacao beans. The presence of partitiviruses was confirmed by sequencing the viral dsRNAs and purifying and visualizing isometric, non-enveloped viral particles. ScPVs have a typical bipartite genome encoding an RNA-dependent RNA polymerase (RdRP) and a coat protein (CP). Phylogenetic analysis of ScPVs identified three species of ScPV, which are most closely related to viruses of the genus Cryspovirus from the mammalian pathogenic protozoan Cryptosporidium parvum . Molecular modeling of the ScPV RdRP revealed a conserved tertiary structure and catalytic site organization when compared to the RdRPs of the Picornaviridae . The ScPV CP is the smallest so far identified in the Partitiviridae and has structural homology with the CP of other partitiviruses but likely lacks a protrusion domain that is a conspicuous feature of other partitivirus particles. ScPVs were stably maintained during laboratory growth and were successfully transferred to haploid progeny after sporulation, which provides future opportunities to study partitivirus-host interactions using the powerful genetic tools available for the model organism S . cerevisiae .

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Influenza A viral burst size from thousands of infected single cells using droplet quantitative PCR (dqPCR)

An important aspect of how viruses spread and infect is the viral burst size, or the number of new viruses produced by each infected cell. Surprisingly, this value remains poorly characterized for influenza A virus (IAV), commonly known as the flu. In this study, we screened tens of thousands of cells using a microfluidic method called droplet quantitative PCR (dqPCR). The high-throughput capability of dqPCR enabled the measurement of a large population of infected cells producing progeny virus. By measuring the fully assembled and successfully released viruses from these infected cells, we discover that the viral burst sizes for both the seasonal H3N2 and the 2009 pandemic H1N1 strains vary significantly, with H3N2 ranging from 10 1 to 10 4 viruses per cell, and H1N1 ranging from 10 1 to 10 3 viruses per cell. Some infected cells produce average numbers of new viruses, while others generate extensive number of viruses. In fact, we find that only 10% of the single-cell infections are responsible for creating a significant portion of all the viruses. This small fraction produced approximately 60% of new viruses for H3N2 and 40% for H1N1. On average, each infected cell of the H3N2 flu strain produced 709 new viruses, whereas for H1N1, each infected cell produced 358 viruses. This novel method reveals insights into the flu virus and can lead to improved strategies for managing and preventing the spread of viruses.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

Genomic Dissection of Anthracnose ( Colletotrichum sublineolum ) Resistance Response in Sorghum Differential Line SC112-14

Sorghum production is expanding to warmer and more humid regions where its production is being limited by multiple fungal pathogens. Anthracnose, caused by Colletotrichum sublineolum , is one of the major diseases in these regions, where it can cause yield losses of both grain and biomass. In this study, 114 recombinant inbred lines (RILs) derived from resistant sorghum line SC112-14 were evaluated at four distinct geographic locations in the United States for response to anthracnose. A genome scan using a high-density linkage map of 3,838 single nucleotide polymorphisms (SNPs) detected two loci at 5.25 and 1.18 Mb on chromosomes 5 and 6, respectively, that explain up to 59% and 44% of the observed phenotypic variation. A bin-mapping approach using a subset of 31 highly informative RILs was employed to determine the disease response to inoculation with ten anthracnose pathotypes in the greenhouse. A genome scan showed that the 5.25 Mb region on chromosome 5 is associated with a resistance response to nine pathotypes. Five SNP markers were developed and used to fine map the locus on chromosome 5 by evaluating 1,500 segregating F 2:3 progenies. Based on the genotypic and phenotypic analyses of 11 recombinants, the locus was narrowed down to a 470-kb genomic region. Following a genome-wide association study based on 574 accessions previously phenotyped and genotyped, the resistance locus was delimited to a 34-kb genomic interval with five candidate genes. All five candidate genes encode proteins associated with plant immune systems, suggesting they may act in synergy in the resistance response.

Genetics & Heredity↗
DOE OSTI2019

The Genetic Basis of Mutation Rate Variation in Yeast

Mutations are the root source of genetic variation and underlie the process of evolution. Although the rates at which mutations occur vary considerably between species, little is known about differences within species, or the genetic and molecular basis of these differences. Here, we leveraged the power of the yeast Saccharomyces cerevisiae as a model system to uncover natural genetic variants that underlie variation in mutation rate. We developed a high-throughput fluctuation assay and used it to quantify mutation rates in seven natural yeast isolates and in 1040 segregant progeny from a cross between BY, a laboratory strain, and RM, a wine strain. We observed that mutation rate varies among yeast strains and is heritable (H 2 = 0.49). We performed linkage mapping in the segregants and identified four quantitative trait loci underlying mutation rate variation in the cross. We fine-mapped two quantitative trait loci to the underlying causal genes, RAD5 and MKT1, that contribute to mutation rate variation. These genes also underlie sensitivity to the DNA-damaging agents 4NQO and MMS, suggesting a connection between spontaneous mutation rate and mutagen sensitivity.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2019

Deleterious Mutation Burden and Its Association with Complex Traits in Sorghum (Sorghum bicolor)

Sorghum (Sorghum bicolor L.) is a major food cereal for millions of people worldwide. The sorghum genome, like other species, accumulates deleterious mutations, likely impacting its fitness. The lack of recombination, drift, and the coupling with favorable loci impede the removal of deleterious mutations from the genome by selection. To study how deleterious variants impact phenotypes, we identified putative deleterious mutations among ~5.5 M segregating variants of 229 diverse biomass sorghum lines. We provide the whole-genome estimate of the deleterious burden in sorghum, showing that ~33% of nonsynonymous substitutions are putatively deleterious. The pattern of mutation burden varies appreciably among racial groups. Across racial groups, the mutation burden correlated negatively with biomass, plant height, specific leaf area (SLA), and tissue starch content (TSC), suggesting that deleterious burden decreases trait fitness. Putatively deleterious variants explain roughly one-half of the genetic variance. However, there is only moderate improvement in total heritable variance explained for biomass (7.6%) and plant height (average of 3.1% across all stages). There is no advantage in total heritable variance for SLA and TSC. The contribution of putatively deleterious variants to phenotypic diversity therefore appears to be dependent on the genetic architecture of traits. Overall, these results suggest that incorporating putatively deleterious variants into genomic models slightly improves prediction accuracy because of extensive linkage. Knowledge of deleterious variants could be leveraged for sorghum breeding through either genome editing and/or conventional breeding that focuses on the selection of progeny with fewer deleterious alleles.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2017

Lesion complexity drives age related cancer susceptibility in human mammary epithelial cells

Exposures to various DNA damaging agents can deregulate a wide array of critical mechanisms that maintain genome integrity. It is unclear how these processes are impacted by one's age at the time of exposure and the complexity of the DNA lesion. To clarify this, we employed radiation as a tool to generate simple and complex lesions in normal primary human mammary epithelial cells derived from women of various ages. We hypothesized that genomic instability in the progeny of older cells exposed to complex damages will be exacerbated by age-associated deterioration in function and accentuate age-related cancer predisposition. Centrosome aberrations and changes in stem cell numbers were examined to assess cancer susceptibility. Our data show that the frequency of centrosome aberrations proportionately increases with age following complex damage causing exposures. However, a dose-dependent increase in stem cell numbers was independent of both age and the nature of the insult. Phospho-protein signatures provide mechanistic clues to signaling networks implicated in these effects. Together these studies suggest that complex damage can threaten the genome stability of the stem cell population in older people. Propagation of this instability is subject to influence by the microenvironment and will ultimately define cancer risk in the older population.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2013

Space‐Plant versus Sward‐Plot Evaluation of Half‐Sib Families to Select Parents for Synthetic Cultivars with Superior Biomass Yield in Lowland Switchgrass

ABSTRACT Switchgrass ( Panicum virgatum L.) needs significant biomass yield improvement for its viable use as bioenergy feedstock. Conventional family evaluation under sward plot is very effective in cultivar improvement, but it is time and resource consuming. Family evaluation under space planting using honeycomb design can reduce time and inputs. The objective of this study was to compare conventional sward‐plot and modified space‐plant evaluation of half‐sib families in their biomass yield gain and resource use. Using same initial set of genotypes selected from ‘Alamo’, two experimental synthetics were developed by the following methods: (i) summer field polycrossing of selected genotypes to produce half‐sibs, half‐sib family evaluation under sward plot conditions (HSSward) at two locations for 2 yr, and polycrossing the five genotypes showing superior half‐sibs to produce the experimental and (ii) greenhouse polycrossing genotypes during the winter to produce half‐sibs, half‐sib family evaluation under space‐plant conditions using honeycomb design (HSSpace) for 2 yr at one location, and polycrossing the five best progeny within the five superior half‐sibs to produce the experimental. The 2 to 3 yr biomass yield performance of two experimentals across five locations demonstrated that both HSSward and HSSpace led to a significant biomass yield gain over Alamo in three and two of the five locations, respectively. The HSSward produced a superior and more stable synthetic across a wide region than HSSpace. However, the HSSpace produced its synthetic a year sooner and was more resource efficient and, under finite resources, it could be a method of choice for cultivar development especially for a narrow geographic region.

Bhandari, H. S.↗